Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia

Rationale: Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility.Objectives: To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study.Methods: We prospectively evaluated 418 premature neonates (gestational age <28 wk), of whom 22% developed bronchopulmonary dysplasia. Two discovery series were created, using a DNA pooling strategy in neonates from white and African ancestry. Polymorphisms associated with the disease were confirmed in an independent replication population. Genes were then explored by fine mapping and associations were replicated in an external Finnish population of 213 neonates. Validated genes expression patterns were studied in rat lung, after air or hyperoxia exposure.Measurements and Main Results: SPOCK2 gene was identified by both discovery series. The most significant polymorphism (rs1245560; P = 1.66 × 10−7) was co...